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Effects of duloxetine on microRNA expression profile in frontal lobe and hippocampus in a mouse model of depression

机译:度洛西汀对抑郁症小鼠模型额叶和海马microRNA表达的影响

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Depression is a major mood disorder affecting people worldwide. The posttranscriptional gene regulation mediated by microRNAs (miRNAs) which may have critical roles in the pathogenesis of depression. However, to date, little is known about the effects of the antidepressant drug duloxetine on miRNA expression profile in chronic unpredictable mild stress (CUMS)-induced depression model in mice. Healthy adult male Kunming mice were randomly divided into three groups: control group, model group and duloxetine group. Sucrose preference test and open field test were used to represent the behavioral change. MiRNAs levels in frontal lobe and hippocampus of mice were analyzed using miRNA microarrays assay. We observed that long-term treatment with duloxetine significantly ameliorated the CUMS procedure-induced sucrose preference decreases and mice treated with duloxetine demonstrated a reversal of the number of crossings, and rearings reduced by CUMS. A significant upregulation of miR-132 and miR-18a in hippocampus in the duloxetine treatment group compared with model group, whereas the levels of miR-134 and miR-124a were significantly downregulated. Furthermore, miR-18a showed significant upregulation in frontal lobe in the duloxetine treatment group relative to model group. Our data showed that miRNA expression profile in frontal lobe and hippocampus was affected by duloxetine in mice model of depression. The effect was especially pronounced in the hippocampus, suggesting that hippocampus might be the action site of duloxetine, which presumably worked by regulating the expression of miRNA levels.
机译:抑郁症是影响世界各地人们的主要情绪障碍。 microRNA(miRNA)介导的转录后基因调控可能在抑郁症的发病机理中起关键作用。然而,迄今为止,关于抗抑郁药度洛西汀对慢性不可预测的轻度应激(CUMS)诱导的小鼠抑郁模型中miRNA表达谱的影响知之甚少。健康的成年雄性昆明小鼠随机分为三组:对照组,模型组和度洛西汀组。蔗糖偏好测试和野外测试被用来代表行为改变。使用miRNA微阵列分析法分析了小鼠额叶和海马中的miRNA水平。我们观察到长期用度洛西汀治疗可显着改善CUMS程序引起的蔗糖偏爱性降低,而用度洛西汀治疗的小鼠表现出交叉次数逆转,CUMS减少了饲养。与模型组相比,度洛西汀治疗组海马中的miR-132和miR-18a明显上调,而miR-134和miR-124a的水平则明显下调。此外,相对于模型组,度洛西汀治疗组中miR-18a的额叶显着上调。我们的数据表明,度洛西汀在抑郁症小鼠模型中影响额叶和海马中的miRNA表达。该作用在海马中尤其明显,表明海马可能是度洛西汀的作用部位,其可能通过调节miRNA的表达起作用。

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